Changes in cannabinoid receptors, aquaporin 4 and vimentin expression after traumatic brain injury in adolescent male mice. Association with edema and neurological deficit

PLoS One. 2015 Jun 3;10(6):e0128782. doi: 10.1371/journal.pone.0128782. eCollection 2015.


Traumatic brain injury (TBI) incidence rises during adolescence because during this critical neurodevelopmental period some risky behaviors increase. The purpose of this study was to assess the contribution of cannabinoid receptors (CB1 and CB2), blood brain barrier proteins (AQP4) and astrogliosis markers (vimentin) to neurological deficit and brain edema formation in a TBI weight drop model in adolescent male mice. These molecules were selected since they are known to change shortly after lesion. Here we extended their study in three different timepoints after TBI, including short (24h), early mid-term (72h) and late mid-term (two weeks). Our results showed that TBI induced an increase in brain edema up to 72 h after lesion that was directly associated with neurological deficit. Neurological deficit appeared 24 h after TBI and was completely recovered two weeks after trauma. CB1 receptor expression decreased after TBI and was negatively correlated with edema formation and behavioral impairments. CB2 receptor increased after injury and was associated with high neurological deficit whereas no correlation with edema was found. AQP4 increased after TBI and was positively correlated with edema and neurological impairments as occurred with vimentin expression in the same manner. The results suggest that CB1 and CB2 differ in the mechanisms to resolve TBI and also that some of their neuroprotective effects related to the control of reactive astrogliosis may be due to the regulation of AQP4 expression on the end-feet of astrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / genetics*
  • Aquaporin 4 / metabolism
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / complications
  • Brain Edema / genetics*
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Brain Injuries / complications
  • Brain Injuries / genetics*
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Cognition Disorders / complications
  • Cognition Disorders / genetics*
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Exploratory Behavior
  • Gene Expression Regulation
  • Male
  • Mice
  • Receptor, Cannabinoid, CB1 / genetics*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / genetics*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Signal Transduction
  • Stereotyped Behavior
  • Vimentin / genetics*
  • Vimentin / metabolism


  • Aqp4 protein, mouse
  • Aquaporin 4
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Vimentin

Grant support

Support was provided by the Ministerio de Economía y Competitividad, Spain (BFU2011-30217-C03-01 and BFU2012-38144), Instituto de Salud Carlos III, Redes temáticas de Investigación Cooperativa en Salud, Red de Trastornos Adictivos (RD2012/0028/0021) and GRUPO UCM (951579). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.